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t(1;19)(q23;p13) TCF3::PBX1

Written2012-07Cristina N Alonso
Hematology-Oncology Department, Hospital Nacional de Pediatria Garrahan, Combate de los Pozos 1881- Zip Code : 1245. Buenos Aires, Republica Argentina
This article is an update of :
1997-10Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers France

(Note : for Links provided by Atlas : click)


ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho 9818/3 B lymphoblastic leukaemia/lymphoma with t(1;19) (q23;p13.3); E2A-PBX1(TCF3-PBX1)
ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 1048
Note Balanced form: -1, -19, +der(1), +der(19); unbalanced form: -19, +der(19).
  t(1;19)(q23;p13) TCF3/PBX1  (A): Unbalanced form: der(19) t(1;19)(q23;p13) G-banding; top - Courtesy Jean-Luc Lai; others - Courtesy Adriana Zamecnikova; and R-banding; top: - Jean Loup Huret, below: - Courtesy Christiane Charrin. (B): Balanced form: t(1;19)(q23;p13) - Courtesy Jean-Luc Lai; bottom: - Courtesy Adriana Zamecnikova. Fluorescence in situ hybridization on metaphases using the LSI TCF3/PBX1 Dual Color, Dual Fusion Translocation Probe (Vysis/Abbott Molecular, US) on (C): normal metaphase and confirming the presence of the TCF3-PBX1 gene fusion on (D): unbalanced der(19)t(1;19)(q23;p13.3) or (E): balanced t(1;19)(q23;p13) - Courtesy Adriana Zamecnikova.

Clinics and Pathology

Disease B Lymphoblastic leukemia/lymphoma with t(1;19)(q23;p13.3); E2A-PBX1 (TCF3-PBX1); mostly found in ALL, L1/L2 type; exceptionally found in L3-like ALL, T-ALL, NHL, or AML.
Phenotype / cell stem origin Most cases: 'pre B' (cIg+) ALL; may be cIg- or sIg+.
CD45dim, CD19pos, CD34neg, CD22pos/dim, CD20dim/pos, CD24pos, TdTpos, CD10neg/dim, cIgMpos, CD9pos, CD15neg, CD65neg, CD66cneg, CD13neg, CD33neg.
Epidemiology 5% of ALL, or 20% of pre B ALL; found in children and young adults (1-60 yrs, median: 10 yrs --> one of the most frequent ALL in childhood (4-6%)); 3 male/4 female patients.
Clinics Moderate organomegaly; frequent CNS involvement; blood data: high WBC (median 20 x 109/L); high LDH.
Treatment Treatment should be adapted to biological features at the moment of diagnosis and also to early chemotherapy response and risk group stratification should not be based on TCF3-PBX1 detection.
Prognosis Although this chromosomal abnormality usually discloses adverse prognostic features (WBC, SNC), it is associated with good prognosis with modern intensive protocols. Median 5 yr-event free survival probability in childhood ALL: 85(6)%; no age or blood data prognostic significance; there are no differences between the prognosis of balanced or unbalanced forms. Prognosis in adults is not different between TCF3-PBX1 positive and negative cases (pEFS: 40 vs. 44%).


Cytogenetics Morphological Breakpoint is in 19p13.3; two different forms (see diagrams above): - the balanced t(1;19), one fourth of cases, with a der(1) and a der(19); - the unbalanced form, found in 3/4 cases, with 2 normal chromosomes 1, a der(19), and 1 normal chromosome 19: --> partial trisomy for 1q23-1qter and monosomy for 19p13.3-pter; the 2 forms can be in mosaic; note: 19p13 and 19q13 may be confused (e.g. literature reports). A subset of ALL usually hyperdyploid B-ALL has an identical t(1;19) that lack the expected phenotype probably do not represent TCF3-PBX1 B-ALL.
Additional anomalies t(17;19)(q22;p13) is not stricto sensu a variant, but, so far, an equivalent, with HLF (hepatic leukemia factor), on 17q22, involved in the translocation. Additional anomalies are found in half of the cases, mostly partial dup (1q), +6, del(6q), +8, i(9q), +17, i(17q), +21.

Genes involved and Proteins

Note The following are (most often) involved, except in some cases lacking the cIg expression:
Gene NamePBX1 (pre-B-cell leukemia homeobox 1)
Location 1q23.3
Note Previously known as "pre-B-cell leukemia transcription factor 1".
  c-PBX1 at 1q23 in normal cells: PAC 1146N1 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Dna / Rna Alternate splicing (variants 1, 2 and 3) (Acc Numbers: NM_001204963.1, NM_001204961.1 and NM_002585.3).
Protein Nuclear protein that belongs to the PBX homeobox family of transcriptional factors. Contains a homeodomain to bind to DNA.
Gene NameTCF3 (transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47))
Location 19p13.3
Note Other names: bHLHb21, E2A, "E2A immunoglobulin enhancer-binding factor E12/E47", E47, "immunoglobulin transcription factor 1", ITF1, "kappa-E2-binding factor", MGC129647, MGC129648, "transcription factor E2-alpha", VDIR, "VDR interacting repressor".
Dna / Rna Alternate splicing 2 isoforms --> E12 and E47. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 9.
Protein Contains transcriptional activation domains and a basic helix-loop-helix DNA binding site; binds specifically to an immunoglobulin enhancer; nuclear localization; transcription factor.

Result of the chromosomal anomaly

Hybrid gene
Description 5' TCF3 exons fused to 3' PBX1; breakpoints are clustered on both genes; the reciprocal 5' PBX1 - 3' E2A is not transcribed.
Transcript Most cases present fusion of exons 1-16 in TCF3 to exons 4-9 in PBX1. Alternative breakpoint in intron 4 of PBX1, not detectable by standardized RT-PCR primers, has been reported.
Fusion Protein
Description 550 amino acids; 85 kDa; N-term transcriptional activation domains from TCF3 fused to the Hox cooperative motif and homeodomain of C-term PBX1; potent transcriptional activator.
Expression Localisation Nuclear localisation.
Oncogenesis Pleiotropic transforming activity. The resulting fusion protein (TCF3-PBX1), in which the DNA binding domain of E2A is replaced by the DNA binding domain of TCF3, transforms cells by constitutively activating transcription of genes regulated by PBX1 or by other members the PBX protein family.


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This paper should be referenced as such :
Alonso, CN
t(1;19)(q23;p13) TCF3/PBX1
Atlas Genet Cytogenet Oncol Haematol. 2013;17(1):45-47.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
Huret, JL. t(1;19)(q23;p13). Atlas Genet Cytogenet Oncol Haematol. 1997;1(2):76-78.

Other genes implicated (Data extracted from papers in the Atlas) [ 3 ]

Genes TCF3 PBX1

Translocations implicated (Data extracted from papers in the Atlas)

 t(1;19)(q23;p13) TCF3/PBX1

External links

TCF3 (19p13.3) PBX1 (1q23.3)

TCF3 (19p13.3) PBX1 (1q23.3)

TCF3 (19p13.3) PBX1 (1q23.3)

Mitelman databaset(1;19)(q23;p13)
COSMICHisto = - Site = haematopoietic_and_lymphoid_tissue (COSMIC)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9818/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9837/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
COSMIC_fusionTCF3/PBX1 TCF3 (19p13.3) PBX1 (1q23.3)   [fusion1489]   [fusion1490]   [fusion2121]   [fusion2122]   [fusion2123]   [fusion2124]   [fusion2125]   [fusion2126]   [fusion2127]   [fusion2128]   [fusion2129]   [fusion2130]   [fusion2131]   [fusion2132]   [fusion2133]   [fusion2134]   [fusion2135]   [fusion2136]   [fusion2137]   [fusion2138]   [fusion2140]   [fusion2141]   [fusion2142]   [fusion2143]   [fusion2144]   [fusion2145]   [fusion2146]   [fusion2147]  
Mitelman databaseTCF3::PBX1 [MCList]  TCF3 (19p13.3) PBX1 (1q23.3)
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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